Aptamers refer to nucleic acids (DNA, RNA, and PNA) having an ability to bind to a specific material. Binding target materials (hereinafter, also referred to as “target material) of the aptamers include a wide variety of materials, for example, biomolecules such as proteins, hormones, and peptides; artificial molecules such as agricultural chemicals; and small molecules such as potassium ions. Therefore, a target material contained in a specimen can be quantitatively measured by detecting a bond between an aptamer and the target material. In addition, a sensor which specifically responds to a target material can be constructed by extracting a bond between an aptamer and the target material as an electric signal.
When a target material is detected using an aptamer, there are advantageous effects in that, for example, an aptamer is easily handled during solution exchange or the like, and a large number of aptamers are easily handled at the same time. Therefore, there are cases where an aptamer may be used while being held on a solid body (for example, Patent Documents 1 and 2 and Non-Patent Documents 1 to 4).
For example, Non-Patent Documents 1 and 2 disclose sensors in which aptamers 101 and 121 labeled with methylene blues, which are electrode reactants 103 and 113, are fixed on electrodes 104 and 114 (FIGS. 1(a) to 1(d)). Using a bond with a target material (a target material 107 such as thrombin or a cocaine 127), these sensors detect conformational changes occurring in the aptamers 101 and 121 as changes in distance between the electrodes 104 and 114 and the electrode reactants 103 and 113, that is, as changes in the reaction currents of the electrode reactants 103 and 113. However, as clearly seen from a schematic diagram of FIG. 1, the pattern and amount of a conformational change of an aptamer caused by a bond with a target material vary depending on aptamers. That is, as illustrated in FIG. 1(c), after a conformational change of the aptamer 121, the electrode reactant 113 may be separated from the electrode 114. On the other hand, as illustrated in FIG. 1(d), after a conformational change of the aptamer 121, the electrode reactant 113 may approach the electrode 114. Therefore, when a distance between a labeling material and an electrode is greatly changed by chance and is used in a sensor with a method disclosed in Non-Patent Documents 1 and 2, an aptamer capable of obtaining a sufficient signal change becomes limited. That is, the techniques of Non-Patent Documents 1 and 2 have a room for improvement in terms of detection accuracy.
Patent Document 1 discloses a technique in which a mechanism for detecting the existence of a target material is improved. That is, Patent Document 1 discloses an aptamer sensor using the aptamer 101 and a complementary strand 102 thereof as illustrated in FIG. 2. According to Patent Document 1, the existence of a target material can be detected according to the following mechanism. That is, in the aptamer sensor, the aptamer 101 and the complementary strand 102 form complementary base pairs to form a double-stranded nucleic acid region (double strand-forming site 105) (FIG. 2(a)) in the absence of the target material. In this double-stranded nucleic acid region, when the target material 107 exists, the formation of the complementary base pairs is dissociated and eliminated (FIG. 2(b)) by the aptamer 101 and the target material 107 binding to each other. By detecting changes in physical and chemical properties caused by the dissociation, the target material is detected. For example, Patent Document 1 discloses that the existence of a target material can be detected by detecting the separation of the complementary strand 102 having the electrode reactant 103 from the electrode 104 (surface plasmon resonance sensor substrate).